1. Field of the Invention
The invention relates to a system and method of preparing Magnetically Actuated Propellers (MAPs) that can be propelled and controlled by magnetic fields for biomedical and rheological applications. The disclosed method, in particular, describes structures which can be produced with typical feature sizes that range in one dimension from more than 20 nanometers to sizes that are below 100 microns in all dimensions. The propellers are made from nano-structured surfaces and can be produced in large numbers.
The invention further describes a propulsion method that uses magnetic fields in order to control and propel MAPs in solutions, suspensions, liquids, and tissue and other soft matter.
2. Description of the Related Art
There is a great interest in the fabrication of structures whose motion can be controlled in liquids or soft matter or tissue or suspensions. There is a need to be able to build and propel artificial robotic swimmers that rival the versatility of biological swimmers of similar size, such as those of motile bacterial cells. Applications for artificial swimmers range from use in complex fluids to diagnostics and targeted drug delivery to microsurgery. It is necessary that the motion of these structures—that are referred to with a number of descriptions, such as “artificial swimmers”, “artificial bacteria”, “propellers”, “micro-bots”, “nano-bots”, etc.—can be made in large numbers and that they can be controlled from a distance and that they can be steered and propelled by a convenient means.
While significant progress has been made in making larger scale objects that can be manipulated in liquids, the difficulty of attaining a high level of control for smaller devices (<mm) is far from trivial, since obtaining any motion at small length scales requires special strategies. The problem has for instance been described by Purcell (E. M. Purcell, “Life at low Reynolds number,” Am. J. Phys. 45, 3-11 (1977)), who described how microorganisms, such as bacteria and spermatozoa achieve locomotion by screw-like and flexible oar-like (non-reciprocal) movements, respectively. The difficulty lies in the fact that the motion of small objects, such as those that are detailed in this invention, is dominated by viscous drag forces (while glide and lift is absent). Low Reynolds number hydrodynamics is described in J. Happel and H. Brenner, Low Reynolds Number Hydrodynamics. (Prentice-Hall, Englewood Cliffs, N.J., 1965). The structures and/or their propulsion method therefore need to permit motion under conditions of low Reynolds number hydrodynamics.
To propel artificial micro- and nano-scale objects, a variety of sources of power, such as electric fields, chemical reactions, and optical forces etc. have been used (Wang Joseph and Manesh Kalayil Manian, “Motion Control at the Nanoscale,” Small 6 (3), 338-345 (2010); Stephen Ebbens and Jonathan Howse, “In pursuit of propulsion at the nanoscale,” Soft Matter (2010); Mirkovic Tihana, S. Zacharia Nicole, D. Scholes Gregory et al., “Nanolocomotion—Catalytic Nanomotors and Nanorotors,” Small 6 (2), 159-167.). These have distinct drawbacks for biomedical applications or rheological applications in complex fluids and suspensions, as electric fields are difficult to apply in aqueous environments, optical forces require transparent media, and chemical reactions often require corrosive environments or special chemicals and are concentration-dependent.
One technique used to maneuver and control the motion of small scale objects in fluidic environments is the optical tweezer (A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm et al., “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11 (5), 288-290 (1986). David G. Grier, “A revolution in optical manipulation,” Nature 424 (6950), 810-816 (2003)), where focused laser beams allow micron sized beads to be trapped and moved in solution. With recent technological developments, large number of beads could now be trapped and moved independently. While this technique has provided invaluable information in many biophysical problems, especially those involving rheological measurements, the optical traps are typically created very close to a microscope objective in an optically transparent sample, while requiring a powerful laser beam. This in turn excludes in-vivo applications, where either proximity to the biological sample or applying a strong laser beam is undesirable, or it excludes applications in complex fluids that are opaque and/or scatter laser light.
Methods, which reply on chemical reactions (R. Kline Timothy, F. Paxton Walter, E. Mallouk Thomas et al., “Catalytic Nanomotors: Remote-Controlled Autonomous Movement of Striped Metallic Nanorods13,” Angewandte Chemie International Edition 44 (5), 744-746 (2005). Shakuntala Sundararajan, Paul E. Lammert, Andrew W. Zudans et al., “Catalytic Motors for Transport of Colloidal Cargo,” Nano Letters 8 (5), 1271-1276 (2008). Jared Burdick, Rawiwan Laocharoensuk, Philip M. Wheat et al., “Synthetic Nanomotors in Microchannel Networks: Directional Microchip Motion and Controlled Manipulation of Cargo,” Journal of the American Chemical Society 130 (26), 8164-8165 (2008).)), typically rely on some form on non-aqueous medium, such as hydrogen peroxide which severely limits their utility and excludes most in-vivo biological applications.
Electric fields have also been used to maneuver mm sized polymer gels and diodes (Y. Osada, H. Okuzaki, and H. Hori, “A polymer gel with electrically driven motility,” Nature 355, 242-244 (1992). Suk Tai Chang, Vesselin N. Paunov, Dimiter N. Petsev et al., “Remotely powered self-propelling particles and micropumps based on miniature diodes,” Nat Mater 6 (3), 235-240 (2007)); but these are only suitable for applications where electrodes can be placed in the sample.
Magnetic fields are less intrusive in most bio-environments and can be used in almost all complex fluids, including opaque and scattering media. Magnetic fields can act on diamagnetic, paramagnetic, and ferromagnetic structures and exert forces on these structures. The forces in turn can in principle be used to orient, align, and/or propel these structures. The detailed response of a structure depends on the magnetic properties of the structure, the nature of the applied magnetic field and the precise geometry of structure and the environment it is in. In the context of actuating and propelling magnetic structures in fluid environments—as described in this invention—paramagnetic, superparamagnetic and ferromagnetic structures interacting with magnetic fields are of importance.
A paramagnetic structure such as a bead can for instance be manipulated with a magnetic tweezer. Magnetic tweezers (F. H. C. Crick and A. F. W. Hughes, “The physical properties of cytoplasm: A study by means of the magnetic particle method Part I. Experimental,” Experimental Cell Research 1 (1), 37-80 (1950).) rely on magnetic field gradients, and so it becomes necessary to arrange for a magnetic field whose strength varies with distance across the structure. This may be achieved with suitable gradient coils. The paramagnetic structure is ‘pulled’ by the magnetic field gradient in the direction of the stronger field lines. An asymmetric paramagnetic structure may also be aligned with a magnetic field.
Ferromagnetic structures can be aligned with a homogenous magnetic field as the magnetic field exerts a torque on a structure with a ferromagnetic moment. It is energetically favorable if the magnetic moment to be parallel to the magnetic field vector and this causes alignment of ferromagnetic moments with the field lines of a magnetic field. If the magnetic field rotates then a moment will follow the magnetic field. A structure that has a magnetic moment will therefore also start to rotate. This is used in the present invention to rotate a screw like object, which exhibits rotation-translation coupling, such that it propels forward (translates). The ferromagnetic structure experiences a torque that varies linearly with the strength of the applied magnetic field.
The advantages of using homogeneous vs. a gradient magnetic field for manipulating nanoparticles have also been considered (Jake J. Abbott, Marco Cosentino Lagomarsino, Li Zhang et al., “How Should Microrobots Swim?,” The International Journal of Robotics Research, 0278364909341658 (2009)). It is also possible to use a combination (Choi Hyunchul and et al., “Two-dimensional actuation of a microrobot with a stationary two-pair coil system,” Smart Materials and Structures 18 (5), 055007 (2009)) of homogeneous and gradient fields to move mm sized permanent magnets. Paramagnetic structures can be “pulled or pushed” with gradient fields.
In order to fabricate structures that respond to and can be manipulated and controlled with magnetic fields materials need to be used that possess suitable magnetic properties (i.e. paramagnetic, superparamagnetic or ferromagnetic) in addition to the structural properties that permit locomotion at low Reynolds numbers. One such structure is for instance a screw or screw-like or helical structure in conjunction with a ferromagnetic moment. Similar to a cork-screw or the flagellum of a bacterial cell, it is chiral, that is, it is handed, and can be propelled in low Reynolds number hydrodynamics by rotation. This invention describes the fabrication of structures that possess a ferromagnetic moment and that can be rotated with a magnetic field and that thereby can be screw-like propelled through solution, liquid, suspensions, tissue, or biological samples etc. by the application of suitable magnetic fields.
Henceforth, the description shall refer to “artificial swimmers”, “artificial bacteria”, “propellers”, “micro-bots”, “nano-bots” or in any structure that is larger than 20 nanometers in any of its dimensions and smaller than 100 microns in its dimensions and that can be propelled with magnetic fields and/or magnetic field gradients as Magnetically Actuated Propellers (MAPs). It is desirable that MAPs can be reproducibly made on a large scale by a fabrication method that is robust, and that can produce a large number of MAPs. Furthermore, for biomedical and rheological applications it is particularly important that the MAP structures can be propelled through solution or biological tissue or suspensions. The present invention describes the fabrication, actuation and propulsion of MAPs whose hydrodynamic properties are described by low Reynolds number hydrodynamics.
Existing methods for making artificial swimmers including MAPs have a number of shortcomings. 3D-lithographic techniques used to make structures that can be propelled from a distance are often limited to fabrication of MAPs on a few square millimeters. Also the ranges of shapes that can be made by these masking techniques are limited. Two-photon lithographic techniques can be used to make three-dimensional structures such as helices, which can in principle be used to realize MAPs, including systems described by this invention, but are time-consuming and in general do not permit the parallel fabrication of large numbers of MAPs. It is therefore more convenient to directly use vacuum deposition techniques that can give rise to structures, which can be used to make MAPs, which is also the preferred embodiment of the present invention.
For example, U.S. Pat. No. 6,304,768, describes a device and a method for using magnetic fields to move different types of magnetic delivery vehicles. Though it is to be noted that the described technique relies on positioning magnets for locating and guiding the magnetic vehicles, which may not work in an efficient manner with the MAPs and the examples of magnetic delivery vehicles as provided are completely different than what has been described in the present invention.
US Patent Application, published as US 2010/0242585 A1, teaches the method of using a device which is an object with no specific dimensions, for drilling mud. The structure of the proposed “nano-robot” is completely different from the MAPs which are the subject of present invention and the proposed applications are only limited to the measurement of mechanical properties of mud and gravel, and has no relation to biomedical applications.
A method for making structures in nanostructured thin films is described, for example, in U.S. Pat. No. 6,206,065, Robbie, K. J., et al. U.S. Pat. No. 6,206,065, however, said patent does not disclose the use of the vapor-deposited thin film for making structures that can be propelled from a distance in low Reynolds number fluids or soft matter including tissues and suspensions, and in particular it does not disclose use of the vapor-deposited thin film for making MAPs, and it does not disclose how to release structures from the substrate, and it does not disclose any rheological and biomedical applications.
While US Patent Application, published as US20110052393 A1, teaches a method of moving a magnetic device at low Reynolds numbers it is to be noted that the described device is different from the MAPs of the present invention, since the essence of the described device requires two interacting magnetic particles.
Further, US Patent Application, published as US 2010/0022857 A1, describes an intraocular sensor, part of which is magnetic. The described sensor geometry is different from the MAPs described in the present invention and is typically much larger than typical sizes in which the MAPs described in the present invention are fabricated. Also, the scope of the application is limited to intraocular measurements.
The US Patent Application, published as U.S. Pat. No. 7,220,310 B2, describes a system of nanobelts made of ZnO which are shaped like a propeller. The method of fabrication described is not as general or versatile as with MAPs of the present invention where various materials, sizes and geometries are easily obtainable, and U.S. Pat. No. 7,220,310 B2 fails to teach how the structure may be propelled (translated).
Crucial to the present invention is that the three-dimensional structure of the MAP permits the propulsion or actuation with a magnetic field such that the MAP can be controllably propelled. The present invention describes a system for fabricating large numbers of MAPs that is based on shadow growth vapor deposition. This invention described a propulsion method that uses magnetic fields in order to control and propel MAPs in solutions, suspensions, liquids, and tissue and other soft matter. Furthermore, the system and method of this invention permits large numbers of these structures to be fabricated simultaneously. Applications are described including but not limited to the diagnosis of diseases, delivery of drug molecules, and in the controlled delivery of MAPs and therefore materials and agents of therapeutic value.
A variety of magnetic materials can be used to accomplish the specific properties required to realize a MAP. For an object of volume, V, and magnetization per unit volume, {right arrow over (M)}, in a magnetic field flux density, {right arrow over (B)}, the applied torque, {right arrow over (T)}, and force, {right arrow over (F)}, are given by {right arrow over (T)}=V{right arrow over (M)}×{right arrow over (B)} and {right arrow over (F)}=V({right arrow over (M)}·{right arrow over (Δ)}){right arrow over (B)} respectively. While gradient fields can pull paramagnetic beads, the usage of homogeneous fields typically requires ferromagnetic character in the MAPs. It is important to consider material properties while designing a ferromagnetic MAP, since ferromagnetic structures show super-paramagnetic behavior, as they become smaller in size. The loss of ferromagnetism is essentially due to the absence of the motion of domain walls at small sizes, where the formation of domain walls becomes energetically unfavorable. Single domain particles are formed below some critical size and as the sizes are reduced further, the system becomes super-paramagnetic. The specific magnetic properties of materials are for instance listed under http://www.kayelaby.npl.co.uk/generalphysics/2—6/2—6—6.html and it is possible to find materials suitable for vacuum deposition and or electrochemical deposition that can be used in conjunction with Glancing Angle Deposition (GLAD).